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| Status |
Public on Apr 10, 2012 |
| Title |
miR-93/106b and their host gene, MCM7, are differentially expressed in leiomyomas and functionally target F3 and IL-8 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
miR-93/106b and their host gene minichromosome maintenance complex component 7 (MCM7) reside at chr7q22, a region frequently rearranged in leiomyomas. We explored the expression of miR-93/106b in leiomyoma and paired myometrium (N=62) from untreated and patients exposed to hormonal therapies (GnRHa, Depo-Provera and oral contraceptives) from African Americans and Caucasians, and their regulatory functions in isolated paired (N=15) leiomyoma and myometrial smooth muscle cells (LSMC and MSMC) and leiomyosarcoma cell line (SKLM-S1). At tissue level leiomyomas expressed significantly lower levels of miR-93 and elevated MCM7 as compared to myometrium with limited racial influence or hormonal exposure on their expression. Assessing the regulatory function of miR-93/106b through doxycycline-inducible lentiviral transduction in microarray analysis, tissue factor (F3) and IL-8 were identified as their possible targets. At tissue level leiomyomas expressed a significantly lower level of F3 and an elevated IL-8 which exhibited an inverse relationship with miR-93, but with limited racial or hormonal influences. Gain-of-function of miR-93/106b in LSMC, MSMC and SKLM-S1 dose-dependently repressed F3 and IL-8 through direct interactions with their respective 3’UTRs and indirectly through F3 repression inhibited IL8, CTGF and PAI-1 expression, confirmed by using siRNA silencing or factor Vlla (FVIIa) activation of F3, as well as reducing the rate of proliferation, while increasing caspase 3/7 activity. We concluded that differential expression of miR-93/106b and their direct and/or indirect regulatory functions on F3, IL-8, CTGF and PAI-1 expression, with key roles in inflammation and tissue turnover may be of significance in the outcome of leiomyoma growth and associated symptoms.
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| Overall design |
Total RNA isolated from TF324 cells transfected with DOX-inducible lentiviral construct carrying miR-106b~25 cluster with and without Dox treatments for 6 days was subjected to gene expression profiling using Sentirx Beadchip Array HumanHT-12_v4.
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| Contributor(s) |
Chuang T, Luo X, Panda H, Chegini N |
| Citation(s) |
22556343 |
| Submission date |
Apr 09, 2012 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Tsai-Der Chuang |
| E-mail(s) |
chuangtsaide@gmail.com
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| Phone |
310-222-1897
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| Organization name |
LA Biomed at UCLA medical center
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| Department |
OB-GYN
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| Lab |
Omid Khorram
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| Street address |
1124 WEST CARSON STREET
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| City |
Torrance |
| State/province |
California |
| ZIP/Postal code |
90502 |
| Country |
USA |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA158405 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE37122_RAW.tar |
26.2 Mb |
(http)(custom) |
TAR |
| GSE37122_non-normalized.txt.gz |
736.3 Kb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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